Ketolide Antibiotics
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Ketolide Antibiotics
Ketolides are antibiotics belonging to the macrolide group. Ketolides are derived from erythromycin by substituting the cladinose sugar with a keto-group and attaching a cyclic carbamate group in the lactone ring. These modifications give ketolides much broader spectrum than other macrolides. Moreover, ketolides are effective against macrolide-resistant bacteria, due to their ability to bind at two sites at the bacterial ribosome as well as having a structural modification that makes them poor substrates for efflux-pump mediated resistance.Bertram G. Katzung, Susan B. Masters, Anthony J. Trevor ''Basic & Clinical Pharmacology, 11e'' McGraw-Hill 2009 via "accessmedicine.com" Ketolides block protein synthesis by binding to ribosomal subunits and may also inhibit the formation of newly forming ribosomes. According to a recent study comparing the action of the classic macrolides erythromycin and azithromycin with ketolides, which are used to treat serious infections, the more power ...
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Telithromycin
Telithromycin is the first ketolide antibiotic to enter clinical use and is sold under the brand name of Ketek. It is used to treat community acquired pneumonia of mild to moderate severity. After significant safety concerns, the US Food and Drug Administration sharply curtailed the approved uses of the drug in early 2007. Telithromycin is a semi-synthetic erythromycin derivative. It is created by substituting a ketogroup for the cladinose sugar and adding a carbamate ring in the lactone ring. An alkyl-aryl moiety is attached to this carbamate ring. Furthermore, the oxygen at the 6 position is methylated, as is the case with clarithromycin, to achieve better acid-stability. It was patented in 1994 and approved for medical use in 2001. Adverse effects Most common side-effects are gastrointestinal, including diarrhea, nausea, abdominal pain and vomiting. Headache and disturbances in taste also occur. Less common side-effects include palpitations, blurred vision, and rashes. ...
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Protein Synthesis
Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside Cell (biology), cells, homeostasis, balancing the loss of cellular proteins (via Proteolysis, degradation or Protein targeting, export) through the production of new proteins. Proteins perform a number of critical functions as enzymes, structural proteins or hormones. Protein synthesis is a very similar process for both prokaryotes and eukaryotes but there are some distinct differences. Protein synthesis can be divided broadly into two phases - Transcription (biology), transcription and Translation (biology), translation. During transcription, a section of DNA encoding a protein, known as a gene, is converted into a template molecule called messenger RNA (mRNA). This conversion is carried out by enzymes, known as RNA polymerases, in the cell nucleus, nucleus of the cell. In eukaryotes, this mRNA is initially produced in a premature form (Primary transcript, pre-mRNA) which undergoes post-tra ...
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Hepatitis
Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pain, and diarrhea. Hepatitis is ''acute'' if it resolves within six months, and '' chronic'' if it lasts longer than six months. Acute hepatitis can resolve on its own, progress to chronic hepatitis, or (rarely) result in acute liver failure. Chronic hepatitis may progress to scarring of the liver (cirrhosis), liver failure, and liver cancer. Hepatitis is most commonly caused by the virus ''hepatovirus A'', '' B'', '' C'', '' D'', and '' E''. Other viruses can also cause liver inflammation, including cytomegalovirus, Epstein–Barr virus, and yellow fever virus. Other common causes of hepatitis include heavy alcohol use, certain medications, toxins, other infections, autoimmune diseases, and non-alcoholic steatohepatitis (NASH). Hepa ...
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Respiratory Tract Infections
Respiratory tract infections (RTIs) are infectious diseases involving the respiratory tract. An infection of this type usually is further classified as an upper respiratory tract infection (URI or URTI) or a lower respiratory tract infection (LRI or LRTI). Lower respiratory infections, such as pneumonia, tend to be far more severe than upper respiratory infections, such as the common cold. Types Upper respiratory tract infection The upper respiratory tract is considered the airway above the glottis or vocal cords; sometimes, it is taken as the tract above the cricoid cartilage. This part of the tract includes the nose, sinuses, pharynx, and larynx. Typical infections of the upper respiratory tract include tonsillitis, pharyngitis, laryngitis, sinusitis, otitis media, certain influenza types, and the common cold. Symptoms of URIs can include cough, sore throat, runny nose, nasal congestion, headache, low-grade fever, facial pressure, and sneezing. Lower respiratory tract infectio ...
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Bacterial Pneumonia
Bacterial pneumonia is a type of pneumonia caused by bacterial infection. Types Gram-positive ''Streptococcus pneumoniae'' () is the most common bacterial cause of pneumonia in all age groups except newborn infants. ''Streptococcus pneumoniae'' is a Gram-positive bacterium that often lives in the throat of people who do not have pneumonia. Other important Gram-positive causes of pneumonia are '' Staphylococcus aureus'' () and '' Bacillus anthracis''. Gram-negative Gram-negative bacteria are seen less frequently: ''Haemophilus influenzae'' (), ''Klebsiella pneumoniae'' (), ''Escherichia coli'' (), ''Pseudomonas aeruginosa'' (), ''Bordetella pertussis'', and ''Moraxella catarrhalis'' are the most common. These bacteria often live in the gut and enter the lungs when contents of the gut (such as vomit or faeces) are inhaled. Pneumonia caused by ''Yersinia pestis'' is usually called pneumonic plague. Atypical Atypical bacteria causing pneumonia are ''Coxiella burnetii'', ''Chlam ...
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Solithromycin
Solithromycin (trade name Solithera) is a ketolide antibiotic undergoing clinical development for the treatment of community-acquired pneumonia and other infections. Solithromycin exhibits excellent ''in vitro'' activity against a broad spectrum of Gram-positive respiratory tract pathogens, including macrolide-resistant strains. Solithromycin has activity against most common respiratory Gram-positive and fastidious Gram-negative pathogens, and is being evaluated for its utility in treating gonorrhea. Pre-clinical studies An ''in vivo'' pre-clinical study performed by Jeffrey Keelan done in sheep may provide a prophylactic approach for intrauterine infections during pregnancy. This study was carried out by administering solithromycin to pregnant sheep, resulting in effective concentrations greater than 30 ng/ml in the fetal plasma, maternal plasma and amniotic fluid. A single maternal dose maintained these concentrations for over 12 hours. Clinical trials *May 2011: solit ...
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Cethromycin
Cethromycin, trade name Restanza (initially known as ABT-773) is a ketolide antibiotic undergoing research for the treatment of community acquired pneumonia (CAP) and for the prevention of post-exposure inhalational anthrax, and was given an "orphan drug" status for this indication. Originally discovered and developed by Abbott, it was acquired by Advanced Life Sciences Inc. for further development. On October 1, 2008 Advanced Life Sciences submitted a New Drug Application (NDA) to Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ... (FDA) for cethromycin to treat mild-to-moderate community acquired pneumonia. On December 3, 2008 Advanced Life Sciences announced that this New Drug Application has been accepted for filing by the FDA. In June 2009, an ...
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Telithromycin
Telithromycin is the first ketolide antibiotic to enter clinical use and is sold under the brand name of Ketek. It is used to treat community acquired pneumonia of mild to moderate severity. After significant safety concerns, the US Food and Drug Administration sharply curtailed the approved uses of the drug in early 2007. Telithromycin is a semi-synthetic erythromycin derivative. It is created by substituting a ketogroup for the cladinose sugar and adding a carbamate ring in the lactone ring. An alkyl-aryl moiety is attached to this carbamate ring. Furthermore, the oxygen at the 6 position is methylated, as is the case with clarithromycin, to achieve better acid-stability. It was patented in 1994 and approved for medical use in 2001. Adverse effects Most common side-effects are gastrointestinal, including diarrhea, nausea, abdominal pain and vomiting. Headache and disturbances in taste also occur. Less common side-effects include palpitations, blurred vision, and rashes. ...
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Azithromycin
Azithromycin, sold under the brand names Zithromax (in oral form) and Azasite (as an eye drop), is an antibiotic medication used for the treatment of a number of bacterial infections. This includes middle ear infections, strep throat, pneumonia, traveler's diarrhea, and certain other intestinal infections. Along with other medications, it may also be used for malaria. It can be taken by mouth or intravenously. Common side effects include nausea, vomiting, diarrhea and upset stomach. An allergic reaction, such as anaphylaxis, QT prolongation, or a type of diarrhea caused by ''Clostridium difficile'' is possible. No harm has been found with its use during pregnancy. Its safety during breastfeeding is not confirmed, but it is likely safe. Azithromycin is an azalide, a type of macrolide antibiotic. It works by decreasing the production of protein, thereby stopping bacterial growth. Azithromycin was discovered in 1980 by the Yugoslav pharmaceutical company Pliva and approved f ...
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Ribosome
Ribosomes ( ) are macromolecular machines, found within all cells, that perform biological protein synthesis (mRNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA (mRNA) molecules to form polypeptide chains. Ribosomes consist of two major components: the small and large ribosomal subunits. Each subunit consists of one or more ribosomal RNA (rRNA) molecules and many ribosomal proteins (RPs or r-proteins). The ribosomes and associated molecules are also known as the ''translational apparatus''. Overview The sequence of DNA that encodes the sequence of the amino acids in a protein is transcribed into a messenger RNA chain. Ribosomes bind to messenger RNAs and use their sequences for determining the correct sequence of amino acids to generate a given protein. Amino acids are selected and carried to the ribosome by transfer RNA (tRNA) molecules, which enter the ribosome and bind to the messenger RNA chain via an anti-c ...
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Antibiotic
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of such infections. They may either kill or inhibit the growth of bacteria. A limited number of antibiotics also possess antiprotozoal activity. Antibiotics are not effective against viruses such as the common cold or influenza; drugs which inhibit viruses are termed antiviral drugs or antivirals rather than antibiotics. Sometimes, the term ''antibiotic''—literally "opposing life", from the Greek roots ἀντι ''anti'', "against" and βίος ''bios'', "life"—is broadly used to refer to any substance used against microbes, but in the usual medical usage, antibiotics (such as penicillin) are those produced naturally (by one microorganism fighting another), whereas non-antibiotic antibacterials (such as sulfonamides and antiseptics) ...
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